Systemic lupus erythematosus is a chronic relapsing autoimmune disease of unclear etiology. The heterogeneity and unpredictable course of lupus, and the lack of reliable biomarkers to assist in predicting disease flares add to the challenge faced by physicians treating patients with this complex systemic disease. Our data suggest that a demethylated CD4+CD28+KIR+CD11a hi T cell subset correlates with disease activity in lupus patients. Since T cell DNA demethylation is more pronounced in active compared to inactive lupus patients, and because demethylation precedes T cell activation, we hypothesize that the size of the CD4+CD28+KIR+CD11a hi T cells subset correlates with disease activity in lupus and will be a useful biomarker to predict disease flares in lupus patients. We will test this hypothesis using a cross sectional and a longitudinal multicenter collaborative approach. We propose to determine the relationship between CD4+CD28+KIR+CD11a hi T cell subset expansion, total genetic risk, and the SLEDAI score in lupus patients, and to test the CD4+CD28+KIR+CD11a hi T cell subset size as a novel prognostic biomarker for disease progression and remission in a multicenter longitudinal study.